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Smith LR, Wloch MK, Chaplin JA, et al. Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial. Vaccines (Basel). 2013;1(4):398-414doi: 10.3390/vaccines1040398.
Smith, L. R., Wloch, M. K., Chaplin, J. A., Gerber, M., & Rolland, A. P. (2013). Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial. Vaccines, 1(4), 398-414. https://doi.org/10.3390/vaccines1040398
Smith, Larry R, et al. "Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial." Vaccines vol. 1,4 (2013): 398-414. doi: https://doi.org/10.3390/vaccines1040398
Smith LR, Wloch MK, Chaplin JA, Gerber M, Rolland AP. Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial. Vaccines (Basel). 2013 Sep 25;1(4):398-414. doi: 10.3390/vaccines1040398. PMID: 26344340; PMCID: PMC4494211.
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Vaccines (Basel). 2013 Sep 25;1(4):398-414. doi: 10.3390/vaccines1040398.

Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial.

Vaccines

Larry R Smith, Mary K Wloch, Jennifer A Chaplin, Michele Gerber, Alain P Rolland

Affiliations

  1. Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. [email protected].
  2. Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. [email protected].
  3. Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. [email protected].
  4. Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL 60062, USA. [email protected].
  5. Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. [email protected].

PMID: 26344340 PMCID: PMC4494211 DOI: 10.3390/vaccines1040398

Abstract

2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine's planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV⁺) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV⁺ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.

Keywords: CMV end organ disease (EOD); benzalkonium chloride (BAK); cytomegalovirus (CMV); glycoprotein B (gB); hematopoietic cell transplant (HCT); phosphoprotein 65 (pp65); plasmid DNA vaccine; poloxamer CRL1005

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